The Experts below are selected from a list of 50754 Experts worldwide ranked by ideXlab platform
Juliana M Mcelrath - One of the best experts on this subject based on the ideXlab platform.
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hepatitis c virus specific Cytolytic t cell responses after antiviral therapy
Clinical Immunology, 2003Co-Authors: Chihiro Morishima, David R Gretch, Luwy Musey, Marnie Elizaga, Kersten Gaba, Megan Allison, Robert L Carithers, Juliana M McelrathAbstract:Abstract Antigen-specific T cells are likely to provide a critical defense against hepatitis C virus (HCV) infection. However, their detection in blood is uncommon except in persons who undergo spontaneous recovery after acute HCV infection. We postulated that virological responses after antiviral interferon-α therapy may be associated with enhanced Cytolytic T cell immunity. Peripheral blood memory CTL responses were quantified using short term limiting dilution culture, with Cytolytic function detected by standard chromium release assay. In this cross-sectional study, 5 of 11 interferon-α or interferon-α plus ribavirin-treated subjects exhibited Cytolytic T cell responses after therapy completion; 4 of these 5 subjects were HCV RNA negative at the time of assay. In contrast, only 1 of 9 untreated chronically viremic subjects had detectable HCV-specific Cytolytic T cell responses. Although the requisite factors necessary to achieve sustained virologic response after therapy remain largely undefined, the findings presented here suggest that antiviral therapy-induced virological clearance may be associated with the induction, expansion, and/or recirculation of HCV antigen-specific Cytolytic T cells, and may play a role in the maintenance of a nonviremic state.
Paul H Schlesinger - One of the best experts on this subject based on the ideXlab platform.
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Cytolytic peptide nanoparticles (‘NanoBees’) for cancer therapy
Wiley Interdisciplinary Reviews-nanomedicine and Nanobiotechnology, 2011Co-Authors: Hua Pan, Gregory M Lanza, Paul H Schlesinger, Neelesh R. Soman, Samuel A WicklineAbstract:Cytolytic peptides are an attractive class of anticancer candidates because of their wide-spectrum lytic properties. However, their therapeutic potential cannot be realized without a proper delivery vehicle, because of their off-target toxicity, nonspecificity, and unfavorable pharmacokinetics. The physical properties of perfluorocarbon (PFC)-core surfactant-coated nanoparticles render them a highly promising delivery vehicle for targeted therapeutic applications of Cytolytic peptides. This article provides an overview of the mechanism underlying the anticancer efficacy of Cytolytic peptides, the limitations in clinic applications, and the advantages of PFC nanoparticles over traditional FDA-approved nanocarriers such as liposomes. Recent reports of successful anticancer therapeutics delivered by PFC nanoparticles will be discussed, as well as new applications. WIREs Nanomed Nanobiotechnol 2011 3 318–327 DOI: 10.1002/wnan.126 For further resources related to this article, please visit the WIREs website
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molecularly targeted nanocarriers deliver the Cytolytic peptide melittin specifically to tumor cells in mice reducing tumor growth
Journal of Clinical Investigation, 2009Co-Authors: Neeleesh R Soman, Steven L Baldwin, Jon N Marsh, Gregory M Lanza, John E Heuser, Jeffrey Arbeit, Samuel A Wickline, Paul H SchlesingerAbstract:The in vivo application of Cytolytic peptides for cancer therapeutics is hampered by toxicity, nonspecificity, and degradation. We previously developed a specific strategy to synthesize a nanoscale delivery vehicle for Cytolytic peptides by incorporating the nonspecific amphipathic Cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle. Here, we have demonstrated that the favorable pharmacokinetics of this nanocarrier allows accumulation of melittin in murine tumors in vivo and a dramatic reduction in tumor growth without any apparent signs of toxicity. Furthermore, direct assays demonstrated that molecularly targeted nanocarriers selectively delivered melittin to multiple tumor targets, including endothelial and cancer cells, through a hemifusion mechanism. In cells, this hemifusion and transfer process did not disrupt the surface membrane but did trigger apoptosis and in animals caused regression of precancerous dysplastic lesions. Collectively, these data suggest that the ability to restrain the wide-spectrum lytic potential of a potent Cytolytic peptide in a nanovehicle, combined with the flexibility of passive or active molecular targeting, represents an innovative molecular design for chemotherapy with broad-spectrum Cytolytic peptides for the treatment of cancer at multiple stages.
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synthesis and characterization of stable fluorocarbon nanostructures as drug delivery vehicles for Cytolytic peptides
Nano Letters, 2008Co-Authors: Neelesh R. Soman, Gregory M Lanza, Paul H Schlesinger, John M Heuser, Samuel A WicklineAbstract:The therapeutic potential of Cytolytic peptides is plagued by nonspecificity and enzymatic degradation. We report the first stable incorporation of melittin (a 26 amino acid amphipathic peptide) into an outer lipid monolayer of perfluorocarbon nanoparticles. Melittin binds avidly to the nanoparticles (dissociation constant ∼3.27 nM) and retains its pore-forming activity after contact-mediated delivery to model bilayer membrane (liposomes) thereby demonstrating the effectiveness of perfluorocarbon nanoparticles as unique nanocarriers for Cytolytic peptides.
Chihiro Morishima - One of the best experts on this subject based on the ideXlab platform.
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decreased nk cell frequency in chronic hepatitis c does not affect ex vivo Cytolytic killing
Hepatology, 2006Co-Authors: Chihiro Morishima, Denise M Paschal, Chia C Wang, Christina S Yoshihara, Brent L Wood, Scott S Emerson, Margaret C Shuhart, David R GretchAbstract:Prior studies have suggested that natural killer (NK) cell function might be impaired in chronic hepatitis C virus (HCV) infection. Circulating NK cell frequency and Cytolytic activity were examined freshly ex vivo in HCV-infected and uninfected subjects. Surprisingly, the intrinsic Cytolytic activity of peripheral blood NK-enriched cells was similar between HCV-infected and uninfected groups (P = .91). Although the percentage of circulating CD3−CD16/56+NK cells was 30% lower in HCV-infected compared with uninfected subjects (P = .02) paralleled by a decrease of CD56dim Cytolytic NK cells (P = .02), overall K562 cytolysis by unfractionated peripheral blood mononuclear cells was not affected (P = .29). Analysis of the relationships between NK Cytolytic activity and other clinical information revealed an inverse association with liver fibrosis stage (P = .035). In conclusion, NK cell Cytolytic function does not appear to be impaired in chronic hepatitis C, but higher levels of NK cell cytolysis are associated with less liver fibrosis. (HEPATOLOGY 2006;43:573–580.)
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hepatitis c virus specific Cytolytic t cell responses after antiviral therapy
Clinical Immunology, 2003Co-Authors: Chihiro Morishima, David R Gretch, Luwy Musey, Marnie Elizaga, Kersten Gaba, Megan Allison, Robert L Carithers, Juliana M McelrathAbstract:Abstract Antigen-specific T cells are likely to provide a critical defense against hepatitis C virus (HCV) infection. However, their detection in blood is uncommon except in persons who undergo spontaneous recovery after acute HCV infection. We postulated that virological responses after antiviral interferon-α therapy may be associated with enhanced Cytolytic T cell immunity. Peripheral blood memory CTL responses were quantified using short term limiting dilution culture, with Cytolytic function detected by standard chromium release assay. In this cross-sectional study, 5 of 11 interferon-α or interferon-α plus ribavirin-treated subjects exhibited Cytolytic T cell responses after therapy completion; 4 of these 5 subjects were HCV RNA negative at the time of assay. In contrast, only 1 of 9 untreated chronically viremic subjects had detectable HCV-specific Cytolytic T cell responses. Although the requisite factors necessary to achieve sustained virologic response after therapy remain largely undefined, the findings presented here suggest that antiviral therapy-induced virological clearance may be associated with the induction, expansion, and/or recirculation of HCV antigen-specific Cytolytic T cells, and may play a role in the maintenance of a nonviremic state.
Samuel A Wickline - One of the best experts on this subject based on the ideXlab platform.
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Cytolytic peptide nanoparticles (‘NanoBees’) for cancer therapy
Wiley Interdisciplinary Reviews-nanomedicine and Nanobiotechnology, 2011Co-Authors: Hua Pan, Gregory M Lanza, Paul H Schlesinger, Neelesh R. Soman, Samuel A WicklineAbstract:Cytolytic peptides are an attractive class of anticancer candidates because of their wide-spectrum lytic properties. However, their therapeutic potential cannot be realized without a proper delivery vehicle, because of their off-target toxicity, nonspecificity, and unfavorable pharmacokinetics. The physical properties of perfluorocarbon (PFC)-core surfactant-coated nanoparticles render them a highly promising delivery vehicle for targeted therapeutic applications of Cytolytic peptides. This article provides an overview of the mechanism underlying the anticancer efficacy of Cytolytic peptides, the limitations in clinic applications, and the advantages of PFC nanoparticles over traditional FDA-approved nanocarriers such as liposomes. Recent reports of successful anticancer therapeutics delivered by PFC nanoparticles will be discussed, as well as new applications. WIREs Nanomed Nanobiotechnol 2011 3 318–327 DOI: 10.1002/wnan.126 For further resources related to this article, please visit the WIREs website
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molecularly targeted nanocarriers deliver the Cytolytic peptide melittin specifically to tumor cells in mice reducing tumor growth
Journal of Clinical Investigation, 2009Co-Authors: Neeleesh R Soman, Steven L Baldwin, Jon N Marsh, Gregory M Lanza, John E Heuser, Jeffrey Arbeit, Samuel A Wickline, Paul H SchlesingerAbstract:The in vivo application of Cytolytic peptides for cancer therapeutics is hampered by toxicity, nonspecificity, and degradation. We previously developed a specific strategy to synthesize a nanoscale delivery vehicle for Cytolytic peptides by incorporating the nonspecific amphipathic Cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle. Here, we have demonstrated that the favorable pharmacokinetics of this nanocarrier allows accumulation of melittin in murine tumors in vivo and a dramatic reduction in tumor growth without any apparent signs of toxicity. Furthermore, direct assays demonstrated that molecularly targeted nanocarriers selectively delivered melittin to multiple tumor targets, including endothelial and cancer cells, through a hemifusion mechanism. In cells, this hemifusion and transfer process did not disrupt the surface membrane but did trigger apoptosis and in animals caused regression of precancerous dysplastic lesions. Collectively, these data suggest that the ability to restrain the wide-spectrum lytic potential of a potent Cytolytic peptide in a nanovehicle, combined with the flexibility of passive or active molecular targeting, represents an innovative molecular design for chemotherapy with broad-spectrum Cytolytic peptides for the treatment of cancer at multiple stages.
-
synthesis and characterization of stable fluorocarbon nanostructures as drug delivery vehicles for Cytolytic peptides
Nano Letters, 2008Co-Authors: Neelesh R. Soman, Gregory M Lanza, Paul H Schlesinger, John M Heuser, Samuel A WicklineAbstract:The therapeutic potential of Cytolytic peptides is plagued by nonspecificity and enzymatic degradation. We report the first stable incorporation of melittin (a 26 amino acid amphipathic peptide) into an outer lipid monolayer of perfluorocarbon nanoparticles. Melittin binds avidly to the nanoparticles (dissociation constant ∼3.27 nM) and retains its pore-forming activity after contact-mediated delivery to model bilayer membrane (liposomes) thereby demonstrating the effectiveness of perfluorocarbon nanoparticles as unique nanocarriers for Cytolytic peptides.
David R Gretch - One of the best experts on this subject based on the ideXlab platform.
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decreased nk cell frequency in chronic hepatitis c does not affect ex vivo Cytolytic killing
Hepatology, 2006Co-Authors: Chihiro Morishima, Denise M Paschal, Chia C Wang, Christina S Yoshihara, Brent L Wood, Scott S Emerson, Margaret C Shuhart, David R GretchAbstract:Prior studies have suggested that natural killer (NK) cell function might be impaired in chronic hepatitis C virus (HCV) infection. Circulating NK cell frequency and Cytolytic activity were examined freshly ex vivo in HCV-infected and uninfected subjects. Surprisingly, the intrinsic Cytolytic activity of peripheral blood NK-enriched cells was similar between HCV-infected and uninfected groups (P = .91). Although the percentage of circulating CD3−CD16/56+NK cells was 30% lower in HCV-infected compared with uninfected subjects (P = .02) paralleled by a decrease of CD56dim Cytolytic NK cells (P = .02), overall K562 cytolysis by unfractionated peripheral blood mononuclear cells was not affected (P = .29). Analysis of the relationships between NK Cytolytic activity and other clinical information revealed an inverse association with liver fibrosis stage (P = .035). In conclusion, NK cell Cytolytic function does not appear to be impaired in chronic hepatitis C, but higher levels of NK cell cytolysis are associated with less liver fibrosis. (HEPATOLOGY 2006;43:573–580.)
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hepatitis c virus specific Cytolytic t cell responses after antiviral therapy
Clinical Immunology, 2003Co-Authors: Chihiro Morishima, David R Gretch, Luwy Musey, Marnie Elizaga, Kersten Gaba, Megan Allison, Robert L Carithers, Juliana M McelrathAbstract:Abstract Antigen-specific T cells are likely to provide a critical defense against hepatitis C virus (HCV) infection. However, their detection in blood is uncommon except in persons who undergo spontaneous recovery after acute HCV infection. We postulated that virological responses after antiviral interferon-α therapy may be associated with enhanced Cytolytic T cell immunity. Peripheral blood memory CTL responses were quantified using short term limiting dilution culture, with Cytolytic function detected by standard chromium release assay. In this cross-sectional study, 5 of 11 interferon-α or interferon-α plus ribavirin-treated subjects exhibited Cytolytic T cell responses after therapy completion; 4 of these 5 subjects were HCV RNA negative at the time of assay. In contrast, only 1 of 9 untreated chronically viremic subjects had detectable HCV-specific Cytolytic T cell responses. Although the requisite factors necessary to achieve sustained virologic response after therapy remain largely undefined, the findings presented here suggest that antiviral therapy-induced virological clearance may be associated with the induction, expansion, and/or recirculation of HCV antigen-specific Cytolytic T cells, and may play a role in the maintenance of a nonviremic state.
